Dendritic Spines in Depression: What We Learned from Animal Models

Table 4

The effects of chronic stress on dendritic spines on nucleus accumbens (NAc).

#	Stress	Paradigms	Animals	NAc	Function	Proteins or mRNA	References
1	CRS	10 days	Male D1R and D2R mice	↓ AMPAR/NMDAR ratio in D1R-MSNs via MC4R; induces LTD in D1R-MSN	MC4R activation and LTD in NAc are required for stress-induced anhedonia	MC4Rs, -MSH	[135]
2	CRS	1 h/day for 14 days	Male SD rats	Chronic cannabinoid exposure prevents impaired memory via CB1	CB1/2 receptor agonist prevents CRS-induced-impairment LTP in NAc and in the spatial task	↓ glucocorticoid receptors in the Amg, NAc, PFC, and hippocampus	[121]
3	CUMS	3 stressors/day for 21 days	Male Wistar rats	↑ neuron density in DMS; ↓ neuron density in DLS; ↑ dendritic length in DLS; ↔ spine density in DS			[107]
4	CSDS	10 min/day for 10 days	Male C57/BL6J and CD1		↑ ΔFosB induced by CSDS is required for resilience	↑ ΔFosB in resilience mice	[136]
5	CSDS	10 min/day for 10 days	Male C57/BL6 and CD1		↓ fEPSP in NAc; disrupted NMDAR-dependent LTD in cortico-NAc	↓ NR2B surface and PSD95 in NAc; ↔ NR2A, Syn and NR1	[137]
6	CSDS	5 min/each total 3 times	C57BL/6J and CD1 mice	↑ IκK activity; ↑ thin spine density in MSNs	IκK enhances social avoidance behavior	↑ inhibitor of κB kinase (IκK)	[138]
7	CSDS	10 min/day for 10 days	C57BL6/J and CD1 mice	↑ stubby spine density in MSNs in susceptible mice	↑ frequency of mEPSCs in NAc of susceptible mice	↑ IκB kinase (IκK) in NAc in susceptible mice	[139]
8	CSDS	10 min/day for 10 days	C57BL6/J and CD1 mice	↑ Dnmt3a levels in NAc; ↑ spine density in NAc	Dnmt3a regulates depression-like behaviors	↑ DNA methyltransferases (Dnmt3a)	[140]
9	CSDS	10 min/day for 10 days	Male C57/BL6 and CD1	↑ stubby spine density in MSNs in susceptible mice in a Rac-1-dependent manner	↑ cofilin puncta colocalization with stubby spines	↓ Rac-1 mRNA levels in NAc of susceptible mice; ↓ Rac-1 mRNA levels in NAc of depressed patients	[141]
10	CSDS	10 min/day for 10 days	Male C57/BL6 and CD1	Excitatory transmission at ILT-NAc MSN synapses controls susceptibility to CSDS	↑ AMPAR/NMDAR ratio only at ILT inputs to MSNs of susceptible mice	↑ Vglut22, but not Vglut1 in MSN of susceptible mice	[142]
11	CSDS	10 min/day for 10 days	Male C57/BL6 and CD1	↑ uEPSC amplitude in D1R ↓ uEPSC amplitude in D2R mushroom, not thin spines in NAC MSNs in resilient, but not susceptible mice	CSDS does affect uEPSC amplitude mushroom or thin spines of D1-MSNs or D2-MSNs in susceptible mice		[143]
12	CSDS	10 min/day for 10 days	C57BL6/J and CD1 mice	DNA microarrays; some genes specific to susceptibility in VTA and NAC are identified in susceptible mice	↑ firing in VTA DA neurons in susceptible mice	↑ BDNF, Akt, GSK-3β, and ERK1/2 in NAc of susceptible mice	[144]
13	CSDS	10 min/day for 3 days	Male C57/bl6 and CD1	↓ sIPSC frequency in NAc in control, not stressed mice	↑ sensitivity of striatal GABA synapses to the stimulation of cannabinoid CB1R	CB1R ↓	[145]
14	CSDS	10 min/day for 10 days	Male C57/bl6 and CD1	↑ vHIP-NAc synaptic transmission is prosusceptible; ↓ LTD of vHIP-NAc synaptic transmission is proresilient	vHIP afferents to NAc uniquely regulate susceptibility to CSDS; ↓ activity in vHIP in mice resilient to CSDS		[146]
15	Emotional (ES) and physical stress (PS)	10 min/day for 10 days	Male C57/bl6 adolescent (P35) or adult (P56) and CD1	↑ spine density in NAc in adolescents by ES and PS; ↑ spine density in NAc in adult only by PS		ES and PS ↓ p-ERK2 in adolescents but ↑ p-ERK2 in adult	[147]
16	Prenatal stress		Male and female rats	↑ spine density in NAc			[148]

Syn: synaptophysin. CRS: chronic restraint stress. CUMS: chronic unpredictable mild stress. CIS: chronic immobilization stress. CSDS: chronic social defeat stress. MC4R: melanocortin 4 receptor. DMS: dorsal medium striatum. DLM: dorsal lateral striatum. DS: dorsal striatum. ILT: intralaminar thalamus. MSNs: medium spiny neurons. NAc: nucleus accumbens. vHIP: ventral hippocampus. uEPSCs: unitary excitatory postsynaptic currents. ↔: no change. ↓: decrease. ↑: increase.